Rare variant analysis in UKBB and 100K (GEL) whole-genome sequencing datasets provides strong evidence for shared haplotype in all individuals with the c.278_289delTCTGCCCCGAAG insCCGCCTCCT variant
| UKBB background frequency (n with variant/n without) | UKBB frequency in individuals with UMOD c.278_289delTCTGCCCCGAAG insCCGCCTCCT variant (n with/n total) | P value | GEL background frequency (n with variant/n without) | GEL frequency in individuals with UMOD c.278_289delTCTGCCCCGAAG insCCGCCTCCT variant (n with/n total) | P value | |
| 16:19727140:AAAAG:A | 329/115140 | 5/5 | 5×10–12 | 410/75211 | 16/20 | <1×10−16 |
| 16:20420849:T:G | 424/114716 | 4/5 | 1×10–10 | 228/75073 | 18/20 | <1×10−16 |
| 16:20645695:T:G | 418/114722 | 3/5 | 5×10–7 | 218/75083 | 18/20 | <1×10−16 |
| 16:20794732:T:A | 109/115031 | 4/5 | 4×10–12 | 76/75225 | 18/20 | <1×10−16 |
Five of the nine individuals with c.278_289delTCTGCCCCGAAG insCCGCCTCCT variant in the UKBB had whole-genome sequencing data. Specific rare variants (<0.5% UKBB) in a 1 Mb window around the UMOD indel variant (column 1) were significantly over-represented in carriers of the UMOD variant versus the overall UKBB and 100K cohorts. The location of the variants are shown in figure 3. P values are based on Fisher’s exact test and only one individual from each family was included in the analysis.
GEL, Genomics England Limited; 100K, 100,000 Genomes Project; UKBB, UK Biobank; UMOD, uromodulin.